Search

Purpose: Choosing a surgical approach to treat adolescent idiopathic scoliosis (AIS) is still controversial. To compare the effectiveness and safety of combined anterior-posterior approach to posterior-only approach, we conducted a meta-analysis.Methods: We searched electronic database for relevant studies that compared anterior-posterior approach with posterior approach in AIS. Then data extraction and quality assessment were conducted. We used RevMan 5.1 for data analysis. A random effects model was used for heterogeneous data, while a fixed effect model was used for homogeneous data.Results: A total of ten non-randomized controlled studies involving 872 patients were included. There was no significant difference in Cobb angle (95 % CI -0.33 to 4.91, P = 0.09) and percent-predicted FEV1 (95 % CI -6.79 to 4.54, P = 0.70) between the two groups. In subgroup analysis, the kyphosis angle correction was significantly higher than posterior group in severe subgroup (95 % CI 0.72-6.50, P = 0.01), while no significant difference was found in no-restriction subgroup (95 % CI -2.75 to 5.42, P = 0.52). Patients in posterior group obtained a better percent-predicted FVC than those in anterior-posterior group (95 % CI -13.18 to -4.74, P < 0.0001). Significant less complication rate (95 % CI 2.75-17.49, P < 0.0001), blood loss (95 % CI 363.28-658.91, P < 0.00001), operative time (95 % CI 2.65-3.45, P < 0.00001) and length of hospital stay (95 % CI 1.98-22.94, P = 0.02) were found in posterior group.Conclusions: Posterior-only approach can achieve similar coronal plane correction and percent-predicted FEV1 compared to combined anterior-posterior approach. The posterior approach even does better in sagittal correction in severe AIS patients. Significantly less complication rate, blood loss, operative time, length of hospital stay and better percent-predicted FVC are also achieved by posterior-only approach. Posterior-only approach seems to be effective and safe in treating AIS for experienced surgeons. [ABSTRACT FROM AUTHOR]

The development of research and education. In the first two weeks, the same is accurate, and then a professor involved personally attended the Delft meeting. So, how to change the direction of distance learning. North Star (Polaris) has launched a research-based learning network to improve his education's efficiency, and knowledge poses a direct extension of his past used innovation. Compared with conventional courses, technical facilities more, Example: two computers for student PowerPoint presentations and Harvard small whiteboard, two powerful features for computer projection presentation projector, remote teachers and hall of Delft University of video images, distributed a microphone 50 for student desks discussed for open Delft coordinator hand microphone, a monitor control panel and several techniques, two cameras, focused on the projection wall the combined small webcam, teachers and for remote feedback of a large number of cables. Calendar clock design is called a case of Field-Programmable Gate Array (FPGA)-based digital electronic education programs to create research projects. The project aims to develop a case study of Project-Based Learning (PBL), a case study aimed at electronics/computer engineering students or a new digital circuit designer professor of digital design education. To achieve high-performance support using k-mean algorithm learning support. Calendar clock design is the second in a series of content-rich and engaging examples, designed to enhance use counters, multiplexers, comparators and decoder design skills to accomplish this simultaneously. Another option is to use a Field-Programmable Gate Array (FPGA) device as a hardware accelerator. The application of data mining FPGA hardware accelerators. Three kinds of data mining algorithms: tree classification and regression trees, support vector machine and k-means clustering. [ABSTRACT FROM AUTHOR]

Background: This study employs systematic review and meta-analysis to explore the incidence and characteristics of spinal cord injury (SCI) between 2000 and 2021, aiming to provide the most recent and comprehensive data support for the prevention, diagnosis, treatment, and care of SCI. Methods: Systematic searches were conducted on epidemiological studies of SCI published between January 1, 2000, and March 29, 2024. Meta-analysis, subgroup analysis, meta-regression, publication bias detection, and literature quality assessment were extensively utilized. Results: The pooled results from 229 studies indicated that the overall incidence rate of SCI was 23.77 (95% CI, 21.50–26.15) per million people, with traumatic spinal cord injuries (TSCI) at a rate of 26.48 (95% CI, 24.15–28.93) per million people, and non-traumatic spinal cord injuries (NTSCI) at a rate of 17.93 (95% CI, 13.30-23.26) per million people. The incidence of TSCI exhibited a marked age-related increase and was significantly higher in community settings compared to hospital and database sources. Males experienced TSCI at a rate 3.2 times higher than females. Between 2000 and 2021, the incidence of TSCI remained consistently high, between 20 and 45 per million people, whereas NTSCI incidence has seen a steady rise since 2007, stabilizing at a high rate of 25–35 per million people. Additionally, the incidence of TSCI in developing countries was notably higher than that in developed countries. There were significant differences in the causes of injury, severity, injury segments, gender, and age distribution among the TSCI and NTSCI populations, but the proportion of male patients was much higher than that of female patients. Moreover, study quality, country type, and SCI type contributed to the heterogeneity in the meta-analysis. Conclusions: The incidence rates of different types of SCI remain high, and the demographic distribution of SCI patients is changing, indicating a serious disease burden on healthcare systems and affected populations. These findings underscore the necessity of adopting targeted preventive, therapeutic, and rehabilitative measures based on the incidence and characteristics of SCI. [ABSTRACT FROM AUTHOR]

While Wallerian degeneration (WD) is a crucial pathological process induced with spinal cord injury (SCI), its underlying mechanisms is still understudied. In this study, we aim to assess structural alterations and clinical significance of WD in the cervical cord following SCI using multi-modal magnetic resonance imaging (MRI), which combines T2*-weighted imaging and diffusion tensor imaging (DTI). T2*-weighted images allow segmentation of anatomical structures and the detection of WD on macrostructural level. DTI, on the other hand, can identify the reduction in neuroaxonal integrity by measuring the diffusion of water molecules on the microstructural level. In this prospective study, 35 SCI patients (19 paraplegic and 16 tetraplegic patients) and 12 healthy controls were recruited between July 2020 and May 2022. The hyperintensity voxels in the dorsal column was manually labeled as WD on T2*-weighted images. The mean cross-sectional area (CSA) and mean DTI indexes of WD at the C2 level were calculated and compared between groups. Correlation analysis was used to determine the associations of the magnitude of WD with lesion characteristics and clinical outcomes. Compared with controls, SCI patients showed evident hyperintensity (35/35) and decreased neuroaxonal integrity (p < 0.05) within the dorsal column at the C2 level. A higher neurological level of injury was associated with a larger mean CSA and reduction in neuroaxonal integrity within WD (p < 0.05). Smaller total and dorsal tissue bridges were related to greater mean CSA and lower fractional anisotropy values in WD (p < 0.05), respectively. Moreover, SCI participants with significantly larger CSAs and significantly lower microstructural integrity had worse sensory outcomes (p < 0.05). This comprehensive evaluation of WD can help us better understand the mechanisms of WD, monitor progression, and assess the effectiveness of therapeutic interventions after SCI. [ABSTRACT FROM AUTHOR]

A letter to the editor is response to the article "Comparison of combined anterior-posterior approach versus posterior-only approach in treating adolescent idiopathic scoliosis: a meta-analysis" by Z. Chen is presented.

Introduction: A post-hoc subgroup analysis of prospective collected data in a randomized controlled trial (RCT) of minimally invasive discectomy was conducted, to find out the possible underlying reasons for patients with persistent low back pain (LBP) following surgery. Materials and methods: Patients who were diagnosed with lumbar disc herniation (LDH) and underwent either percutaneous transforaminal endoscopic discectomy or microendoscopic discectomy in our RCT were analyzed. Patients with persistent LBP in 2-year follow-up were compared with the non-LBP patients to determine the underlying reasons. Then, the demographic characteristics, clinical outcomes and radiological parameters of patients with preoperative lumbar facet joint osteoarthritis (LFJOA) were assessed and compared with the non-LFJOA subgroup. Results: 18 patients (8.1%) were reported to have persistent LBP in 2-year follow-up. Significantly higher proportion of preoperative LFJOA were found in the persistent LBP subgroup and was considered to be a risk factor using multivariate analysis. The prevalence of LFJOA is strongly associated with older age, female, high BMI and heavy labor in the LDH population. All of the clinical outcomes including ODI, SF36-PF, SF36-BP, EQ-5D, VAS-back and VAS-leg were worse in LFJOA subgroup in 2-year follow-up. LFJOA subgroup was associated with more adjacent segment degeneration and more lateral recess stenosis. Conclusions: LFJOA is a possible underlying reason for patients with persistent LBP after minimally invasive discectomy. Surgeons should carefully review the preoperative radiological images to find out whether there is LFJOA in the LDH segment, and kindly diminish the expectation of back pain relief for those patients. Trial registration: This trial was registered at ClinicalTrials.gov at November 14, 2013, registration number NCT01997086. (https://clinicaltrials.gov/ct2/show/NCT01997086). [ABSTRACT FROM AUTHOR]

Study Design.: A prospective randomized controlled study. Objective.: To compare the efficacy and safety between percutaneous transforaminal endoscopic discectomy (PTED) and microendoscopic discectomy (MED). Summary of Background Data.: Two kinds of minimally invasive discectomy, PTED and MED, are now widely used for treating lumbar disk herniation (LDH). The long-term comparative results of these two techniques still remained uncertain. Materials and Methods.: In this single-center, open-label, randomized controlled trial, patients were included if they had persistent signs and symptoms of radiculopathy with corresponding imaging-confirmed LDH and were randomly allocated to PTED or MED groups. The primary outcome was the score of Oswestry Disability Index (ODI) and the secondary outcomes included the score of Medical Outcomes Study 36-Item Short-Form Health Survey bodily pain (SF36-BP) and physical function (SF36-PF), European Quality of Life—Five Dimensions (EQ-5D), Visual Analog Scales for back pain (VAS-back) and leg pain (VAS-leg). Results.: A total of 241 patients were accepted to enroll in our randomized controlled trial, of which 119 were randomly assigned to the PTED group, and the rest 122 were assigned to the MED group. A total of 194 out of 241 patients (80.5%) completed the five-year follow-up. PTED group was associated with shorter postoperative in-bed time and length of hospital stay. Both primary and secondary outcomes did not differ significantly between the two treatment groups at each follow-up time point. During the five-year follow-up, seven recurrent cases occurred in PTED and MED groups, respectively. Conclusion.: Over the five-year follow-up period, PTED and MED were both efficacious in the treatment of LDH. The long-term clinical outcomes and recurrent rates were comparable between the treatment groups. PTED represents a more minimally invasive technique with the advantages of rapid recovery. [ABSTRACT FROM AUTHOR]

We aim to determinate the patient acceptable symptom state (PASS) for the Oswestry Disability Index (ODI) score in patients undergoing minimally invasive discectomy for the treatment of lumbar disc herniation. A post hoc analysis of prospectively collected, 2-year follow-up data was conducted. The anchor for determination of PASS was the European Quality of Life Visual Analog Scales question, and the Pearson correlation test was performed to evaluate its validity. The receiver operating characteristics (ROC) curve analysis was conducted to determine the PASS thresholds for ODI and its discriminative ability assessment. Sensitivity analyses were also carried out for alternative definition of PASS, different follow-up periods, and different subgroups. A total of 222 patients (92.1%) completed the 2-year follow-up, 92.8% of whom considered their state to be acceptable. The area under the ROC curve (AUC) were all >0.8, indicating a high discriminative ability. The PASS threshold for the ODI was suggested to be 5 at 6 months (AUC: 0.80; sensitivity: 79.0%, specificity: 73.7%) and 2 years (AUC: 0.98; sensitivity: 90.3%, specificity: 100%) postoperatively. Despite some variations found in different body mass index and baseline ODI subgroups, sensitivity analysis showed that the above-mentioned threshold was robust. An ODI of 5 was noted to be the PASS threshold for patients received minimally invasive discectomy for the treatment of LDH. This ODI threshold was robust, and therefore recommended as the ultimate goal of minimally invasive treatment for LDH, which can help to present results of clinical research at an individual level. [ABSTRACT FROM AUTHOR]

Background: Acute spinal cord injury (SCI) is a devastating result of neurological trauma with subsequent microenvironment dyshomeostasis that induces neurotoxic phenotype acquisition by astrocytes, exacerbating neurological function impairment. Exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) have demonstrated essential therapeutic effects after central nervous system trauma. However, whether hUCMSC-derived exosomes exert therapeutic effects on neurotoxic astrocytes to facilitate SCI function recovery remains unclear. Additionally, the limited efficiency of single exosomes may restrict the optimization of exosomal biological functions. Methods: We first determined that exosomes reduce the deleterious effects of neurotoxic astrocytes in vitro and in vivo. Then, we identified critical functional microRNAs (miRNAs). miR-146a-5p was overexpressed in exosomes, and then, miR-146a-5p-modified exosomes were used to investigate the ability of exosomes to reduce neurotoxic astrocyte effects, preserve neurons and promote neurological function recovery in rats with SCI. Results: Cell counting kit-8 and neurite length analyses revealed that exosomes partially reduced the negative effects of neurotoxic astrocytes on PC12 cell viability and neurites in vitro. The exosomes also attenuated inflammatory responses, reduced the number of neurotoxic astrocytes and preserved neural tissue in rats with SCI. Immunofluorescence assays suggested that the number of neurotoxic astrocytes was rapidly increased by injury, reaching a peak 5 days post-injury (dpi) and returning to the normal level 14dpi. Exosomal miR-146a-5p was identified as the critical functional miRNA. Overexpression of miR-146a-5p in exosomes strengthened the biological function of the exosomes. Therefore, the modified exosomes exerted more powerful therapeutic effects than the unmodified exosomes, reducing the deleterious effects of neurotoxic astrocytes both in vitro and in vivo and promoting locomotor function of the hindlimbs in the rats with SCI. Through a series of gain- and loss-of-function experiments, Traf6 and Irak1 were identified as targets of exosomal miR-146a-5p. Ultimately, we found that miR-146a-5p-modified exosomes exerted their function by targeting Traf6/Irak1/NFκB pathway in neurotoxic astrocytes. Conclusions: In summary, miR-146a-5p-modified exosomes exerted a more powerful effect than unmodified exosomes to promote neurological function recovery in rats with SCI by targeting neurotoxic astrocytes. Therefore, miR-146a-5p-modified exosomes are promising therapeutics for SCI. [ABSTRACT FROM AUTHOR]

Objective: Umbilical cord mesenchymal stem cells (UCMSCs) have great potential in the treatment of spinal cord injury. However, the specific therapeutic effect and optimal transplantation strategy are still unclear. Therefore, exploring the optimal treatment strategy of UCMSCs in animal studies by systematic review can provide reference for the development of animal studies and clinical research in the future. Methods: Databases of PubMed, Ovid-Embase, Web of Science, CNKI, WanFang, VIP, and CBM were searched for the literature in February 11, 2022. Two independent reviewers performed the literature search, identification, screening, quality assessment, and data extraction. Results and Discussion: A total of 40 animal studies were included for combined analysis. In different subgroups, the results of traditional meta-analysis and network meta-analysis were consistent, that is, the therapeutic effect of high-dose (≥ 1 × 106) transplantation of UCMSCs was significantly better than that of low dose (< 1 × 106), the therapeutic effect of local transplantation of UCMSCs was significantly better than that of intravenous transplantation, and the therapeutic effect of subacute transplantation of UCMSCs was significantly better than that of acute and chronic transplantation. However, in view of the inherent risk of bias and limited internal and external validity of the current animal studies, more high-quality, direct comparison studies are needed to further explore the optimal transplantation strategy for UCMSCs in the future. [ABSTRACT FROM AUTHOR]

This study aimed to systematically evaluate the optimal surgical fusion approach for lumbar spondylolisthesis, to provide the latest and most reliable evidence for future clinical practice. A comprehensive search of the PubMed, Ovid-Embase, Web of Science, Cochrane, and Scopus databases was conducted from inception to September 1, 2023, to identify relevant records. Two independent reviewers performed the literature screening, data extraction, and assessment of study quality. Fifteen randomized controlled trials involving 892 patients met the inclusion criteria. The network evidence plot showed that posterolateral fusion and posterior lumbar interbody fusion (PLIF) were the most used fusion techniques. The network meta-analysis results revealed that minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) had a significantly greater improvement in the Oswestry Disability Index (ODI) compared to endoscopic-TLIF, while PLIF had a significantly better fusion effect than posterolateral fusion. Furthermore, no statistically significant differences were observed between other fusion surgeries in terms of improving ODI, fusion rate, complications, or the improvement of visual analog scale-low back pain. The surface under the cumulative ranking curve results indicated that MIS-TLIF had the greatest potential for improving ODI, visual analog scale-low back pain, and complications, while PLIF had the greatest potential for increasing fusion rates. However, the existing selection bias, measurement bias, reporting bias, and publication bias may have reduced the reliability of the meta-analysis results. Among the various fusion surgeries for lumbar spondylolisthesis, MIS-TLIF appears to provide the greatest benefit to patients. However, more high-quality, large-scale studies are needed to further investigate the treatment efficacy of different fusion surgeries for lumbar spondylolisthesis. [ABSTRACT FROM AUTHOR]

Study Design: A retrospective cohort study.Objective: The objective of the study was to develop machine-learning (ML) classifiers for predicting prolonged intensive care unit (ICU)-stay and prolonged hospital-stay for critical patients with spinal cord injury (SCI).Summary Of Background Data: Critical patients with SCI in ICU need more attention. SCI patients with prolonged stay in ICU usually occupy vast medical resources and hinder the rehabilitation deployment.Methods: A total of 1599 critical patients with SCI were included in the study and labeled with prolonged stay or normal stay. All data were extracted from the eICU Collaborative Research Database and the Medical Information Mart for Intensive Care III-IV Database. The extracted data were randomly divided into training, validation and testing (6:2:2) subdatasets. A total of 91 initial ML classifiers were developed, and the top three initial classifiers with the best performance were further stacked into an ensemble classifier with logistic regressor. The area under the curve (AUC) was the main indicator to assess the prediction performance of all classifiers. The primary predicting outcome was prolonged ICU-stay, while the secondary predicting outcome was prolonged hospital-stay.Results: In predicting prolonged ICU-stay, the AUC of the ensemble classifier was 0.864 ± 0.021 in the three-time five-fold cross-validation and 0.802 in the independent testing. In predicting prolonged hospital-stay, the AUC of the ensemble classifier was 0.815 ± 0.037 in the three-time five-fold cross-validation and 0.799 in the independent testing. Decision curve analysis showed the merits of the ensemble classifiers, as the curves of the top three initial classifiers varied a lot in either predicting prolonged ICU-stay or discriminating prolonged hospital-stay.Conclusion: The ensemble classifiers successfully predict the prolonged ICU-stay and the prolonged hospital-stay, which showed a high potential of assisting physicians in managing SCI patients in ICU and make full use of medical resources.Level of Evidence: 3. [ABSTRACT FROM AUTHOR]

Induced pluripotent stem cells (iPSCs) have the potential to differentiate into neural lineages. Salvianolic acid B (Sal B) is a commonly used, traditional Chinese medicine for enhancing neuroprotective effects, and has antioxidant, anti-inflammatory, and antiapoptotic properties. Here, we explore the potential mechanism of Sal B in protecting iPSC-derived neural stem cells (NSCs) against HO-induced injury. iPSCs were induced into NSCs, iPSC-derived NSCs were treated with 50 μM Sal B for 24.5 h and 500 μM HO for 24 h. The resulting effects were examined by flow cytometry analysis, quantitative reverse-transcription polymerase chain reaction, and western blotting. Upon HO exposure, Sal B significantly promoted cell viability and stabilization of the mitochondrial membrane potential. Sal B also visibly decreased the cell apoptotic ratio. In addition, Sal B markedly reduced expression of matrix metalloproteinase (MMP)-2 and -9, and phosphospecific signal transducer and activator of transcription 3 (p-STAT3), and increased the level of tissue inhibitor of metalloproteinase (TIMP)-2 in iPSC-derived NSCs induced by HO. These results suggest that Sal B protects iPSC-derived NSCs against HO-induced oxidative stress. The mechanisms of this stress tolerance may be attributed to modulation of the MMP/TIMP system and inhibition of the STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

Various extracellular factors jointly control a wide variety of neuronal functions. On-demand delivery system provides a platform to integrate multiple signals in one intervention. In this study, we fabricated an electrically controlled drug delivery nanocomposite composed of graphene oxide (GO) deposited inside a poly(3,4-ethylenedioxythiophene) (PEDOT) film. 7,8-dihydroxyflavone (7,8-DHF) was loaded on GO via π-π stacking and consequentially encapsulated into the electrochemically active film during deposition, which was followed by a Dopamine- graft -Chitosan (CD) coating to improve the biocompatibility. 7,8-DHF was released in response to voltage stimulation and the dosage was adjusted by altering the magnitude of stimulation. The on-demand delivery system promoted dorsal root ganglion (DRG) neurite outgrowth, Schwann cell migration, myelination, and synapse transmission. Neuronal mitochondrial biogenesis was enhanced as determined by immunofluorescence staining and gene expression of HSP60, a mitochondrial localized quality control protein. Therefore, we provided an on-demand delivery platform of temporal control and dosage flexibility to integrate multiple signals in the modulation of neural behaviors and functions. [Display omitted] • This study describes an on-demand system that delivers multiple signals to neurons. • As a novel nanocarrier, GO enables 7,8-DHF loaded in the electrochemically active film with PEDOT. • 7,8-DHF release is initiated in response to target dose stimulus by electrical stimulation. • The on-demand delivery system promotes neurite outgrowth, myelination and synapse transmission. • Mitochondrial biogenesis enhanced provides high levels of energy consumption for neurons. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Salvia miltiorrhiza, a well-known traditional Chinese medicine, is commonly used to treat some neurological diseases because of its anti-oxidative, anti-inflammatory and anti-apoptotic properties. We investigate whether Salvia miltiorrhiza can improve the differentiation of induced pluripotent stem cells (iPSCs) into neurons in vitro, and promote iPSCs-derived neural stem cells survival, integrate, and differentiation after their transplantation to the ischemic brain tissues. Materials and methods: Induced pluripotent stem cells were used to differentiate into neural stem cells, and further into neurons in induction medium with various concentrations of Salvia miltiorrhiza. The effects were assessed by immunofluorescence staining, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. iPSC-derived neural stem cells were transplanted into the brains of rats with middle cerebral artery occlusion, immunofluorescence staining was used to evaluate survival, integrate, and differentiation of grafted cells, the functional recovery of the animals was tested by the Longa scores and spontaneous motor activity. Results: Salvia miltiorrhiza (5μg/ml) significantly increased the gene and protein expression of Nestin compared with that in other groups. Microtubule-associated protein 2 (MAP2) expression in induction medium with 5μg/ml Salvia miltiorrhiza was significantly higher than that in the control group. After cells transplantation into the ischemic brain, more grafted MAP2+ cells were found in Salvia miltiorrhiza-treated rats than others at 7 days. Salvia miltiorrhiza-treated rats showed the most remarkable functional recovery at 7 and 14 days. Conclusion: Salvia miltiorrhiza induces differentiation of induced pluripotent stem cells to differentiate into neurons efficiently. The plant provides neuroprotection to implanted cells and improves functional recovery after their transplantation to the ischemic brain tissues. [Copyright &y& Elsevier]

This study sought to investigate the feasibility of using magnetic resonance-magnetic resonance-ultrasound (MR-MR-US) fusion imaging navigation (FIN) with needle tail intelligent positioning (NTIP) to guide puncture in percutaneous transforaminal endoscopic discectomy (PTED). First, in a pig experiment, we found that puncture errors in lumbar intervertebral foramen (LIF) puncture using magnetic resonance-magnetic resonance-ultrasound (MR-MR-US) FIN with NTIP for experienced and novice operators were 2.00 ± 1.00 and 2.57 ± 0.98 mm, respectively (p = 0.231), suggesting this technique was minimally dependent on experience. Then, two experienced surgeons agreed (inter-observer agreement к=0.801) that the quality of MR-MR fusion images was good or sufficient. Finally, we performed PTED in eight patients using MR-MR-US FIN with NTIP, and no significant complications were reported during LIF puncture. Overall, MR-MR-US FIN with NTIP may be a potential application for guiding puncture in PTED, but more clinical studies with a larger sample size are required to further evaluate the advantages of MR-MR-US FIN with NTIP. [ABSTRACT FROM AUTHOR]

Background: Hypertrophy is a critical process for chondrocyte differentiation and maturation during endochondral ossification, which is responsible for the formation of long bone and postnatal longitudinal growth. Increasing evidence suggests that melatonin, an indole hormone, plays a pivotal role in chondrogenesis. However, little is known about the effects of melatonin on the terminal differentiation of chondrocytes. Methods: Mesenchymal stem cell (MSC)-derived chondrocytes generated by a high-density micromass culture system were induced to undergo hypertrophic differentiation. Melatonin-mediated hypertrophic differentiation was examined by reverse transcription polymerase chain reaction analysis (RT-PCR) analysis, histological staining and immunohistochemistry. Activation of the Wnt signaling pathway was evaluated by PCR array, RT-PCR, western blotting and immunofluorescence. XAV-939, a Wnt signaling pathway antagonist, was further used to determine whether the effect of melatonin on chondrocyte hypertrophic differentiation was mediated occurred by activation of Wnt signaling pathway. Results: Histological staining showed melatonin increased chondrocyte cell volume and the expression of type X collagen but decreased the expression of type II collagen compared with the control group. RT-PCR showed that melatonin significantly up-regulated the gene expressions of biomarkers of hypertrophic chondrocytes, including type X collagen, alkaline phosphatase, runt-related transcription factor 2, Indian hedgehog and parathyroid hormone-related protein receptor, and melatonin down-regulated the mRNA expression of hallmarks of chondrocytes, including parathyroid hormone-related protein. PCR array showed that the effect of melatonin on chondrocyte hypertrophic differentiation was accompanied by the up-regulation of multiple target genes of the canonical Wnt signaling pathway, and this effect was blocked by XAV-939. Conclusions: The current findings demonstrate that melatonin enhances the hypertrophic differentiation of MSC-derived chondrocytes through the Wnt signaling pathway. Our findings add evidence to the role of melatonin in promoting bone development and highlight the positive effects of melatonin on terminal differentiation of chondrocytes. [ABSTRACT FROM AUTHOR]

Background: Exosomes derived from the bone marrow mesenchymal stem cell (MSC) have shown great potential in spinal cord injury (SCI) treatment. This research was designed to investigate the therapeutic effects of miR-26a-modified MSC-derived exosomes (Exos-26a) following SCI. Methods: Bioinformatics and data mining were performed to explore the role of miR-26a in SCI. Exosomes were isolated from miR-26a-modified MSC culture medium by ultracentrifugation. A series of experiments, including assessment of Basso, Beattie and Bresnahan scale, histological evaluation, motor-evoked potential recording, diffusion tensor imaging, and western blotting, were performed to determine the therapeutic influence and the underlying molecular mechanisms of Exos-26a in SCI rats. Results: Exos-26a was shown to promote axonal regeneration. Furthermore, we found that exosomes derived from miR-26a-modified MSC could improve neurogenesis and attenuate glial scarring through PTEN/AKT/mTOR signaling cascades. Conclusions: Exosomes derived from miR-26a-modified MSC could activate the PTEN-AKT-mTOR pathway to promote axonal regeneration and neurogenesis and attenuate glia scarring in SCI and thus present great potential for SCI treatment. [ABSTRACT FROM AUTHOR]

Background: Although exosomes, as byproducts of human umbilical cord mesenchymal stem cells (hUC-MSCs), have been demonstrated to be an effective therapy for traumatic spinal cord injury (SCI), their mechanism of action remains unclear. Methods: We designed and performed this study to determine whether exosomes attenuate the lesion size of SCI by ameliorating neuronal injury induced by a secondary inflammatory storm and promoting neurite outgrowth. We determined the absolute levels of all exosomal miRNAs and investigated the potential mechanisms of action of miR-199a-3p/145-5p in inducing neurite outgrowth in vivo and in vitro. Results: miR-199a-3p/145-5p, which are relatively highly expressed miRNAs in exosomes, promoted PC12 cell differentiation suppressed by lipopolysaccharide (LPS) in vitro through modulation of the NGF/TrkA pathway. We also demonstrated that Cblb was a direct target of miR-199a-3p and that Cbl was a direct target of miR-145-5p. Cblb and Cbl gene knockdown resulted in significantly decreased TrkA ubiquitination levels, subsequently activating the NGF/TrkA downstream pathways Akt and Erk. Conversely, overexpression of Cblb and Cbl was associated with significantly increased TrkA ubiquitination level, subsequently inactivating the NGF/TrkA downstream pathways Akt and Erk. Western blot and coimmunoprecipitation assays confirmed the direct interaction between TrkA and Cblb and TrkA and Cbl. In an in vivo experiment, exosomal miR-199a-3p/145-5p was found to upregulate TrkA expression at the lesion site and also promote locomotor function in SCI rats. Conclusions: In summary, our study showed that exosomes transferring miR-199a-3p/145-5p into neurons in SCI rats affected TrkA ubiquitination and promoted the NGF/TrkA signaling pathway, indicating that hUC-MSC-derived exosomes may be a promising treatment strategy for SCI. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the effect of bone marrow mesenchymal stem cell (BMSC)-derived exosome injection on cartilage damage and pain relief in both in vitro and in vivo models of osteoarthritis (OA). Methods: The BMSCs were extracted from rat bone marrow of the femur and tibia. Chondrocytes were treated with IL-1β to establish the in vitro model of OA. Chondrocyte proliferation and migration were assessed by CCK-8 and transwell assay, respectively. A rat model of OA was established by injection of sodium iodoacetate. At 6 weeks after the model was established, the knee joint specimens and dorsal root ganglion (DRG) of rats were collected for histologic analyses. For pain assessment, paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were evaluated before model establishment and at 1, 2, 4, and 6 weeks after model establishment. Results: Exosomes can be endocytosed with the chondrocytes in vitro. Exosome treatment significantly attenuated the inhibitory effect of IL-1β on the proliferation and migration of chondrocytes. Exosome pre-treatment significantly attenuated IL-1β-induced downregulation of COL2A1 and ACAN and upregulation of MMP13 and ADAMTS5. In the animal study, exosome treatment significantly upregulated COL2A1 protein and downregulated MMP13 protein in the cartilage tissue of the OA rat. At weeks 2, 4, and 6, the PWL value was significantly improved in the exosome-treated OA rats as compared with the untreated OA animals. Moreover, exosome treatment significantly alleviated the upregulation of CGRP and iNOS in the DRG tissue of OA rats. Conclusion: BMSC-derived exosomes can effectively promote cartilage repair and extracellular matrix synthesis, as well as alleviate knee pain in the OA rats. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a high‐morbidity skeletal disease worldwide and the exact mechanisms underlying OA pathogenesis are not fully understood. Casein kinase 1 epsilon (CK1ε) is a serine/threonine protein kinase, but its relationship with OA is still unknown. We demonstrated that CK1ε was upregulated in articular cartilage of human patients with OA and mice with experimentally induced OA. Activity of CK1ε, demonstrated by analysis of phosphorylated substrates, was significantly elevated in interleukin (IL)‐1β‐induced OA‐mimicking chondrocytes. CK1ε inhibitor or CK1ε short hairpin RNA (shRNA) partially blocked matrix metalloproteinase (MMP) expression by primary chondrocytes induced by IL‐1β, and also inhibited cartilage destruction in knee joints of experimental OA model mice. Conversely, overexpression of CK1ε promoted chondrocyte catabolism. Previous studies indicated that CK1ε was involved in canonical Wnt/β‐catenin signaling and noncanonical Wnt/c‐Jun N‐terminal kinase (JNK) signaling pathway. Interestingly, the activity of JNK but not β‐catenin decreased after CK1ε knockdown in IL‐1β‐treated chondrocytes in vitro, and JNK inhibition reduced MMP expression in chondrocytes overexpressing CK1ε, which illustrated that CK1ε‐mediated OA was based on JNK pathway. In conclusion, our results demonstrate that CK1ε promotes OA development, and inhibition of CK1ε could be a potential strategy for OA treatment in the future. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency has long been studied as a risk factor for osteoporosis. However, the association between serum vitamin D status, bone mineral density (BMD) and the incidence of vertebral fractures (OVFs) remain controversial. It is believed that free portion of the circulating vitamin D carries the metabolic activities of vitamin D. Therefore, the aim of the present study is to analyse if free vitamin D correlates with BMD and osteoporotic fragile vertebral fractures in the elderly population.Methods: A total of 90 consecutive patients, including 81 female and 9 male patients, aged > 48 years, were included in this cross sectional study between March and July of 2018. Total vitamin D (total 25(OH)D), free vitamin D (free 25(OH)D), calcium and phosphorus were measured. BMD was measured using dual energy X-ray absorptiometry (DEXA) and osteoporotic vertebral fracture was assessed using plain radiograph. Multiple linear regression was performed to find out the association between total vitamin D, free vitamin D and BMD at various sites. To evaluate the association with osteoporotic vertebral multivariate logistic regression model was used.Results: The mean total vitamin D and free vitamin D were 25.1 ± 10.2 and 6.1 ± 1.7 respectively. Free vitamin D had a linear correlation with total vitamin D (R2 = 0.69). While free vitamin D had a positive correlation with lumbar BMD roles (p < 0.05), total vitamin D didn't have any association with BMD at any site. Of the total patients, 62 patients (68.9%) had thoracolumbar junction OVFs. Free vitamin D level correlated with the prevalence of OVFs as well as lumbar osteoporosis (p < 0.05). However, there was no statistical correlation between serum vitamin D status and the OVFs.Conclusions: Free vitamin D was significantly related to the occurrence of thoracolumbar junction OVFs and lumbar BMD, which assumed to be a positive predictor for fracture and osteoporosis prevention. However, total serum vitamin D levels did not have any association with BMD at different sites as well as fragile vertebral fracture.Trial Registration: The study is registered at clinicaltrials.gov NCT03605173. [ABSTRACT FROM AUTHOR]

Smith‒Magenis syndrome (SMS, OMIM: 182290) is a multiple congenital anomalies and intellectual disability syndrome due to a 3.45 Mb microdeletion involving 17p11.2 and is estimated to occur about one in 25,000 births. Up to now, the ultrasound findings of the foetus with SMS and their external genital defects in patients are rarely reported. This case indicates that foetus with SMS may present polyhydramnios and ventriculomegaly in the second trimester. The newborn male patient had an abnormal phenotype in which he has micropenis and his anus is close to the perineal body. The identification of this case may further expand the phenotypic spectrum of this genetic disorder. [ABSTRACT FROM AUTHOR]

Background: Amyloid β peptide (Aβ) is involved in osteoporosis, but the effects of Aβ on osteoblast and bone formation remain unclear. In this study, we investigated the effect of Aβ on bone formation. Methods: An animal model of osteoporosis was established by ovariectomy in C57BL/6 mice. The mice received intraperitoneal injection of Aβ. The effect of Aβ on the osteogenic differentiation of human bone marrow stromal stem cells (hBMSCs) and differentiation of both pre‐osteoblasts and pre‐osteoclasts in a co‐culture system were investigated. Results: In the animal study, intraperitoneal injection of Aβ for 8 weeks promoted early and late osteogenic differentiation of hBMSCs. Aβ treatment significantly elevated osterix+ (osteoblastic) cells but decreased TRAP+ cells (osteoclasts) in the distal femur bone. In vitro study showed that Aβ treatment significantly enhanced matrix mineralization and osteogenic markers (Runx2 and osteocalcin). Aβ treatment activated Wnt/β‐catenin signaling in hBMSCs. The effect of Aβ was blocked by DKK1 (a Wnt/β‐catenin inhibitor) treatment. In the co‐culture system, Aβ treatment significantly increased the ALP activities of MC3T3‐E1 cells (pre‐osteoblasts) but reduced the TRAP+ RAW264.7 cells (pre‐osteoclasts). Aβ treatment upregulated TCF1 and OPG proteins in MC3T3‐E1 cells. Aβ treatment upregulated IκB‐α but downregulated NFATc1protein in RAW264.7 cells. These effects were blocked by XAV‐939 (a Wnt signaling antagonist), and then rescued by additional Wnt3a (a Wnt agonist). Conclusion: Aβ treatment simultaneously promoted osteogenic differentiation via Wnt/β‐catenin signaling, and inhibited osteoclasts differentiation via the OPG/RANKL/RANK system, suggesting Aβ is a positive regulator of osteoblast differentiation and bone formation. [ABSTRACT FROM AUTHOR]

Background: Cordocentesis in our practice is most commonly indicated for rapid karyotyping in the second or third trimester and is regarded as the gold standard for foetal chromosomal aberration diagnosis in pregnancies at high risk for chromosomal abnormalities. In this study, we investigated 3387 umbilical cord blood samples for karyotyping from pregnant women who underwent cordocentesis and explored the pregnancy outcomes of foetal sex chromosome mosaicism and chromosomal polymorphism. Results: Out of the 3387 samples, 182 abnormal karyotypes were detected. Ultrasound soft markers were the most common prenatal diagnostic indication, but the detection rate of abnormal karyotypes was 2.02%, while it was 46.97% in the genome-wide NIPT-positive group. The rate of aneuploidy was lower in the soft marker group than in the other groups. Out of 16 cases with sex chromosome mosaicism, three pregnant women with foetuses with a lower proportion of sex chromosome mosaicism delivered healthy foetuses; the foetus with karyotype 46,X,i(Y)(q10)[20]/45,X[6] showed unclear genitals. Three foetuses with chromosomal polymorphisms had postnatal disorders. Conclusions: NIPT should not be recommended as the first-tier screening for chromosomal aberration for pregnancies with ultrasound soft markers or pathological ultrasound findings, but NIPT can be considered an acceptable alternative for pregnancies with contraindications to cordocentesis or the fear of procedure-related foetal loss. Mosaicism found in amniotic fluid cell culture requires further cordocentesis for karyotype confirmation, and the continuation of pregnancy is safe when a normal karyotype is identified in foetal blood culture. Further genetic testing and parental karyotype analysis are needed for foetal chromosomal polymorphisms. [ABSTRACT FROM AUTHOR]

This pilot study aimed to investigate the feasibility of non-invasively assessing synovial tissue hypoxia in vivo using photoacoustic (PA) imaging in a post-traumatic osteoarthritis model and explore its correlation with OA severity. The three-dimensional vasculature structure and oxygenation level of synovial tissues of destabilization of the medial meniscus (DMM)-induced osteoarthritis (OA) mice were longitudinally monitored using PA imaging. Vascular volume/tissue volume (%) and tissue oxygen saturation (sO 2) were validated against results obtained by established Power Doppler (PD) imaging and dynamic changes of inhaled O 2 concentration respectively. PA changes were correlated with the histological grading of cartilage damages. PA-measurements of vascularity and sO 2 demonstrated a strong correlation with localized blood flow detected by PD imaging (r = 0.506, p < 0.001) and inhaled O 2 concentration. DMM knees exhibited much more vascularity in synovial tissue at 4 months after surgery (median 11.3%, IQR: 10.7–15.5%) than the intact knees at time zero (median:5.1%, IQR:3.8–6.8%, p < 0.001) as well as the sham-operated knees (median: 4%, IQR: 3.75–5.45%, p = 0.017). Paradoxically, synovial tissue sO 2 was significantly lower in DDM knees (median: 37.7%, IQR: 36.4–40.6%) than both the intact (47.1%, IQR: 41.9–49.8% p = 0.001) and sham-operated knees (45.1% IQR: 45.1–52.4%, p = 0.017). The PA-detected synovial tissue hypoxia correlated with the severity of cartilage loss in DMM mice (rho = −0.597, p = 0.031). Here, we demonstrated PA imaging can be implemented for non-invasive imaging of the synovial tissue. Under PA imaging, synovitis in OA was characterized by increased angiogenesis and synovial tissue hypoxia; the latter was associated with the severity of OA. [ABSTRACT FROM AUTHOR]

Quantitative fluorescence polymerase chain reaction (QF-PCR) may be used as a mid-pregnancy test to confirm the diagnosis of common fetal aneuploidies, but its use is controversial. The present study aimed to determine the value of QF-PCR for diagnostic confirmation of karyotyping and the impact of parental origin and meiosis stage on the detected aneuploidy. The present prospective cohort study included pregnant women (age, 21–45 years; gestational age, 17–25 weeks) who consulted between May 2015 and December 2016. Women were screened and only consecutive high-risk individuals were included (n=428). QF-PCR analysis of amniocytes was performed. Karyotype analysis was considered the gold standard. Parental karyotyping was performed if the embryo exhibited any aneuploidy. GeneMapper 3.2 was used for data analysis. There were no false-negative or false-positive QF-PCR results, with 100% concordance with the karyotype. The aneuploidy distribution (n=105) was 68.6% for trisomy 21, 19.0% for trisomy 18, 7.6% for sex chromosome aneuploidy, 3.8% for trisomy 13 and 1.0% for 48,XXX,+18. Regarding trisomy 21, most cases (86.1%) were of maternal origin, 8.3% paternal and 6.5% undefined. Trisomy 18 was 88.2% maternal and 11.8% paternal. Maternal meiosis stage errors in trisomy 21 mainly occurred in meiosis I, while the origin of trisomy 18 exhibited similar proportions between meiosis I and II. The combination of non-invasive pre-natal testing and QF-PCR may become a rapid and effective method for fetal aneuploidy detection. QF-PCR may provide more genetic information for clinical diagnosis and treatment than karyotyping alone. [ABSTRACT FROM AUTHOR]

Long noncoding RNA (lncRNAs) UCA1 has been known to be critical for the chondrogenic differentiation of marrow mesenchymal stem cells (MSCs). In this study, we explore the effects and mechanisms of UCA1 on the promotion of chondrogenesis of MSCs. During the processes of chondrogenic differentiation of MSCs, UCA1, miRNA-145-5p or miRNA-124-3p was overexpressed into MSCs. UCA1 substantially improved chondrogenesis of MSCs. Furthermore, UCA1 obviously down-regulated the expression of miRNA-145-5p and miRNA-124-3p, which attenuated the chondrogenic differentiation of MSCs. In addition, UCA1 significantly stimulated TGF-β pathway member SMAD5 and SMAD4, which is targeted by miRNA-145-5p and miRNA-124-3p. Collectively, these outcomes suggest that UCA1 enhances chondrogenic differentiation of MSCs via the miRNA-145-5p/SMAD5 and miRNA-124-3p/SMAD4 axis. • UCA1 promoted the chondrogenic differentiation of MSCs. • UCA1 down-regulated miRNA-145-5p/miRNA-124-3p during this process. • miRNA-145-5p targeted SMAD5 and miRNA-124-3p targeted SMAD4. [ABSTRACT FROM AUTHOR]

Abstract: Bone marrow‐derived mesenchymal stem cells (BMSCs), with inherent chondrogenic differentiation potential appear to be ideally suited for therapeutic use in cartilage regeneration. Accumulating evidence has demonstrated that melatonin can promote chondrogenic differentiation in human BMSCs. However, little is known about the mechanism. MicroRNAs (miRNAs) have been shown to regulate the differentiation of BMSCs, but their roles in melatonin‐promoted chondrogenic differentiation have not been characterized. Here, we demonstrate that melatonin promoted chondrogenic differentiation of human BMSCs via upregulation of miR‐526b‐3p and miR‐590‐5p. Mechanistically, the elevated miR‐526b‐3p and miR‐590‐5p enhanced SMAD1 phosphorylation by targeting SMAD7. Additionally, administration of miR‐526b‐3p mimics or miR‐590‐5p mimics successfully promoted the chondrogenic differentiation of human BMSCs. Collectively, our study suggests that modification of BMSCs using melatonin or miRNA transduction could be an effective therapy for cartilage damage and degeneration. [ABSTRACT FROM AUTHOR]

Melatonin is a neurohormone mainly extracted from the pineal gland with neuroprotective effects. It has antioxidant, anti-inflammatory, and antiapoptotic functions. However, the mechanism of melatonin against reactive oxygen species is unclear. Here, we explore the potential proliferative and neuroprotective mechanism of melatonin on induced pluripotent stem cells (iPSC)-derived neural stem cells (NSCs) exposed to hydrogen peroxide (H 2 O 2 ). NSCs were induced from iPSCs, then pretreated with 500 μM H 2 O 2 , 1 μM melatonin, 1 μM melatonin receptor antagonist (Luzindole), or 10 μM Phosphatidylinositide 3 kinase (PI3K) inhibitor (LY294002). The results showed that melatonin stimulated proliferation of iPSC-derived NSCs on H 2 O 2 exposure. Melatonin also markedly improved stabilization of the mitochondrial membrane potential and reduced the rate of apoptosis. Treatment with Luzindole or LY294002 inhibited the increasing proliferative and neuroprotective effects of melatonin on iPSC-derived NSCs with H 2 O 2 treatment. Our results further demonstrated that these promotional effects of melatonin were related with the activity of phosphorylation of AKT. Therefore, these outcomes propose that melatonin protects iPSC-derived NSCs from H 2 O 2 -induced injury through the mediation of melatonin receptor and PI3K/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Salvianolic acid B (Sal B), a water-soluble component mainly extracted from the traditional Chinese medicine Salvia miltiorrhiza, has potential anti-inflammatory, anti-oxidative and anti-apoptotic actions to protect neural cells. Here, we explore the effects and mechanisms of Sal B on the promotion of differentiation of induced pluripotent stem cells (iPSCs) into neural stem cells (NSCs), then further into neurons. During the processes of neural differentiation of iPSCs, Sal B or a phosphatidylinositide 3 kinase (PI3K) inhibitor (LY294002) were added to the medium. Sal B substantially improved proliferation of iPSC-derived NSCs and neurons. Furthermore, Sal B significantly stimulated PI3K/AKT/GSK3 β/β-catenin pathway. However, LY294002 attenuated the Sal B-induced increase. Therefore, these outcomes suggest that Sal B markedly enhances neural differentiation of iPSCs via the PI3K/AKT/GSK3β/β-catenin pathway. [ABSTRACT FROM AUTHOR]

Induced pluripotent stem cells (iPSCs) possess the potential to differentiate into neural lineage cells. Matrix metalloproteinase 2 (MMP2), an endopeptidase in the extracellular matrix, has been shown to protect neural cells from injury. However, the mechanisms and effects of MMP2 on neural differentiation of iPSCs remain poorly understood. Here, we demonstrated a role for MMP2 in the differentiation of iPSCs to neurons via the AKT pathway. Treatment of iPSCs with MMP2 promoted their proliferation and differentiation into neural stem cells (NSCs), and then into neurons. The transcript and protein expression of Nestin and microtubule-associated protein 2 (MAP2) increased. Moreover, MMP2 markedly induced the expression of phospho-AKT (pAKT) during these differentiation stages. Consistently, silencing MMP2 using siRNA attenuated the expression of Nestin, MAP2 and pAKT, compared with the control group. In addition, the increasing levels of Nestin, MAP2 and pAKT in the MMP2 group were declined by pretreatment with the phosphoinositide 3-kinase (PI3K)/AKT inhibitor, LY294002. Furthermore, the study detected that TrkA and TrkB were perhaps the potential receptors for these effects of MMP2 on neural differentiation through PI3K/AKT signaling pathway. Taken together, these results suggest that MMP2 induces the differentiation of iPSCs into neurons by regulating the AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Hidden haemorrhage has been proved to be significant in joint surgery. However, when referring to lumbar interbody fusion, it is often ignored because of its invisibility. This randomized controlled study aimed to calculate and compare hidden haemorrhage following minimally invasive and open transforaminal lumbar interbody fusion (MIS-TLIF and open TLIF). Meanwhile, its clinical significance was also analyzed.Materials and Methods: A total of 41 patients were included in this study, then they were randomized to receive MIS-TLIF or open TLIF, 21 and 20, respectively. For each case, total volume loss of red blood cell (RBC) was calculated by Gross' formula based on perioperative haematocrit change, then perioperative visible volume loss of RBC was calculated through haemorrhage volume and weight. After deducting it from total volume loss of RBC, hidden volume loss of RBC was obtained. Absolute amount of hidden haemorrhage and its ratio upon total haemorrhage, as well as indicators assessing clinical outcomes, including visual analogue scale (VAS) for back and leg, Oswestry disability index (ODI), interbody fusion rate and complication incidence were compared and analyzed.Results: Mean hidden volume loss of RBC in MIS-TLIF was significantly reduced compared with open TLIF (166.7 versus 245.6 ml). Besides, both mean total and visible volume loss of RBC in MIS-TLIF were also statistically less than those in open TLIF (355.3 versus 538.6 ml; 188.6 versus 293.0 ml). While mean ratio of hidden haemorrhage upon total haemorrhage was 46.7% for MIS-TLIF and 44.5% for open TLIF, respectively, showing no statistical significance. At one week postoperatively, more significant improvements of VAS for back and leg, as well as ODI were seen in MIS-TLIF compared with open TLIF. While at final follow-up of at least 2 years, all parameters continued to improve and revealed no statistical difference between both surgeries. Similar interbody fusion rate and complication incidence were observed in both series.Conclusions: Besides reduced visible haemorrhage and improved clinical outcomes, MIS-TLIF also owns the superiority of less hidden haemorrhage, offering another advantage over open TLIF.Level Of Evidence: Level II. [ABSTRACT FROM AUTHOR]

Aim. To investigate the feasibility and effectiveness of intraoperative myelography in determining adequacy of indirect spinal canal decompression during transpsoas lateral lumbar interbody fusion (LLIF). Methods. Seven patients diagnosed with degenerative lumbar spinal stenosis (DLSS) were prospectively included to this study. All patients underwent LLIF and subsequently received intraoperative myelography to determine the effect of indirect spinal canal decompression, which was visualized in both anterior-posterior and lateral images. Those patients with insufficient indirect canal decompression were further resolved by microendoscopic canal decompression (MECD). Radiological parameters, including stenosis ratio and dural sac area of operated levels, were measured and compared before and after operation. Besides, all patients were followed up for at least one year using visual analogue scale (VAS) for back and leg, Japanese Orthopaedic Association score (JOA), and Oswestry disability index (ODI). Results. Seven patients with 8 operated levels underwent LLIF safely and demonstrated significant symptom relief postoperatively. Five operated levels showed adequate indirect canal decompression intraoperatively, while the remaining three levels did not achieve the adequacy, and their residual stenosis was resolved following MECD. Radiological parameters were improved statistically when compared with preoperation (P<0.05). Furthermore, neurological symptoms of all patients were also improved significantly (P<0.05), shown by improved VAS (back and leg), JOA, and ODI at both two-week and one-year follow-up. Conclusions. Intraoperative myelography during LLIF is able to assess adequacy of indirect canal decompression for DLSS, thus promising favorable clinical outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Using MR imaging, nerve root sedimentation sign (SedSign) was demonstrated to have a high sensitivity and specificity for diagnosis of symptomatic lumbar spinal stenosis (LSS) in selected patients. This study was to evaluate the diagnostic value of SedSign in differential diagnosis of LSS and non-specific low back pain (LBP) in consecutive patients.Methods: A series of consecutive patients with lumbar spinal MRI examination for back/leg pain in orthopeadic clinic were included. These patients were followed up and divided into two groups, symptomatic LSS and non-specific LBP, according to symptoms and radiological findings. Using MR images, SedSign was assessed by two spine surgeons and one radiologist independently. Then sensitivity and specificity of SedSign was calculated.Result: A total of 320 patients (105 LSS and 215 non-specific LBP) were included. The SedSign had a sensitivity of 77.1 % and specificity of 47.0 % in the whole cohort. When these patients were stratified by dural sac cross-sectional areas (CSA), the SedSign had a sensitivity of 95.0 % and specificity of 4.7 % in patients with CSA ≤ 80 mm2 (severe radiologic stenosis), sensitivity of 74.2 % and specificity of 22.6 % in patients with CSA 80-100 mm2 (moderate radiologic stenosis), and sensitivity of 58.8 % and specificity of 61.0 % in patients with CSA 100-120 mm2 (mild radiologic stenosis). In selected cases composed by LSS patients with CSA ≤ 80 mm2 and non-specific LBP patients with CSA > 120 mm2, however, the SedSign had a sensitivity of 95.0 % and specificity of 80.0 %.Conclusion: The present data demonstrated that the SedSign was not able to discriminate symptomatic LSS from non-specific LBP after adjusting by dural sac CSA. The diagnostic value of the SedSign was still uncertain. [ABSTRACT FROM AUTHOR]

• Different chondrocyte subpopulations exist in OA patients. • The prevalence of different chondrocyte subpopulations shifts during the pathology of OA. • Stress-metabolizing chondrocytes are dominant in early cartilage damage and the matrix-synthesis-related chondrocytes are dominant in late stages. • NFKBIA and TUBB2B are as potential markers for the stress-metabolizing chondrocytes and the matrix synthesis related chondrocytes, respectively. Osteoarthritis (OA) is the most common joint disease. Previous studies were focused on general functions of chondrocyte population in OA without elucidating the existence of chondrocyte subpopulations. To investigate the heterogeneity of chondrocyte, here we conducted detailed analysis on the single-cell sequencing data of cartilage cells from OA patients. After quality control, unsupervised K-mean clustering identified seven different subpopulations of chondrocytes in OA. Those subpopulations of chondrocytes were nominated based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis: stress-metabolizing chondrocytes (cluster 1), rhythmic chondrocytes (cluster 2), apoptotic chondrocytes (cluster 3), matrix-synthesis-related chondrocytes (cluster 4), developmental chondrocytes (cluster 5), protein-synthesis-related chondrocytes (cluster 6 and 8), and osteogenesis chondrocytes (cluster 7). We further noticed that the stress-metabolizing chondrocytes (cluster 1) were dominant in early stages of cartilage damage with increased metabolic levels inhibiting cartilage tissue degeneration, while the matrix-synthesis-related chondrocytes (cluster 4) were mainly existed in the late stages of cartilage damage which reorganized collagen fibers with type III collagen disrupting the extracellular matrix and further cartilage damages. Besides, we identified genes NFKBIA and TUBB2B as potential markers for the stress-metabolizing chondrocytes and the matrix synthesis related chondrocytes, respectively. Our study identifies different chondrocyte subpopulations in OA, and highlights the potential different functions of chondrocyte subpopulations in the early versus late stages of cartilage damage. [ABSTRACT FROM AUTHOR]

Osteoporosis and Alzheimer's disease (AD) are common chronic degenerative disorders which are strongly associated with advanced age. We have previously demonstrated that amyloid beta peptide (Aβ), one of the pathological hallmarks of AD, accumulated abnormally in osteoporotic bone specimens in addition to having an activation effect on osteoclast (Bone 2014,61:164-75). However, the underlying molecular mechanisms remain unclear. Activation of NF-κB, extracellular signal-regulated kinase (ERK) phosphorylates, and calcium oscillation signaling pathways by receptor activator NF-κB ligand (RANKL) plays a pivotal role in osteoclast activation. Targeting this signaling to modulate osteoclast function has been a promising strategy for osteoclast-related diseases. In this study, we investigated the effects of Aβ on RANKL-induced osteoclast signaling pathways in vitro. In mouse bone marrow monocytes (BMMs), Aβ exerted no effect on RANKL-induced osteoclastogenesis but promoted osteoclastic bone resorption. In molecular levels, Aβ enhanced NF-κB activity and IκB-α degradation, activated ERK phosphorylation and stimulated calcium oscillation, thus leading to upregulation of NFAT-c1 expression during osteoclast activation. Taken together, our data demonstrate that Aβ enhances RANKL-induced osteoclast activation through IκB-α degradation, ERK phosphorylation, and calcium oscillation signaling pathways and that Aβ may be a promising agent in the treatment of osteoclast-related disease such as osteoporosis. [ABSTRACT FROM AUTHOR]

Melatonin, a lipophilic molecule mainly synthesized in the pineal gland, has properties of antioxidation, anti-inflammation, and antiapoptosis to improve neuroprotective functions. Here, we investigate effects and mechanisms of melatonin on neural differentiation of induced pluripotent stem cells (iPSCs). iPSCs were induced into neural stem cells (NSCs), then further differentiated into neurons in medium with or without melatonin, melatonin receptor antagonist (Luzindole) or Phosphatidylinositide 3 kinase (PI3K) inhibitor (LY294002). Melatonin significantly promoted the number of neurospheres and cell viability. In addition, Melatonin markedly up-regulated gene and protein expression of Nestin and MAP2. However, Luzindole or LY294002 attenuated these increase. The expression of pAKT/AKT were increased by Melatonin, while Luzindole or LY294002 declined these melatonin-induced increase. These results suggest that melatonin significantly increased neural differentiation of iPSCs via activating PI3K/AKT signaling pathway through melatonin receptor. [ABSTRACT FROM AUTHOR]

The mechanistic target of rapamycin (mTOR) integrates both intracellular and extracellular signals to regulate cell growth and metabolism. However, the role of mTOR signaling in osteoblast differentiation and bone formation is undefined, and the underlying mechanisms have not been elucidated. Here, we report that activation of mTOR complex 1 (mTORC1) is required for preosteoblast proliferation; however, inactivation of mTORC1 is essential for their differentiation and maturation. Inhibition of mTORC1 prevented preosteoblast proliferation, but enhanced their differentiation in vitro and in mice. Activation of mTORC1 by deletion of tuberous sclerosis 1 (Tsc1) in preosteoblasts produced immature woven bone in mice due to excess proliferation but impaired differentiation and maturation of the cells. The mTORC1-specific inhibitor, rapamycin, restored these in vitro and in vivo phenotypic changes. Mechanistically, mTORC1 prevented osteoblast maturation through activation of the STAT3/p63/Jagged/Notch pathway and downregulation of Runx2. Preosteoblasts with hyperactive mTORC1 reacquired the capacity to fully differentiate and maturate when subjected to inhibition of the Notch pathway. Together, these findings identified the role of mTORC1 in osteoblast formation and established that mTORC1 prevents preosteoblast differentiation and maturation through activation of the Notch pathway. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the diagnostic value of the nerve root sedimentation sign, a relatively new radiological sign using magnetic resonance imaging, for diagnosing lumbar spinal stenosis. Materials and methods: The literature search was based on PUBMED, EMBASE, Cochrane Library, Google Scholar, and the Chinese Biomedical Literature Database up to March 2014. A total of 120 articles were identified. Seven studies involving 1,182 patients were included. Results: The quality of the methodology of the seven studies was good. Overall, the pooled weighted value showed that the sedimentation sign had moderate sensitivity of 0.80 [95 % confidence interval (CI) 0.77-0.83] and high specificity of 0.96 (95 % CI 0.94-0.98). The area under the curve was 0.76. Subgroup analysis showed that the degree of morphological spinal stenosis was responsible for the heterogeneity. In the patients with severe morphological lumbar spinal stenosis, the sedimentation sign had even higher sensitivity and specificity: 0.899 (95 % CI 0.87-0.92) and 0.99 (95 % CI 0.98-1.00), respectively. The area under the curve was 0.96. In the patients with lumbar spinal stenosis without definition of morphological stenosis, there was a notable threshold effect and significant heterogeneity. The area under the curve was 0.63. Conclusion: Current evidence suggests that the sedimentation sign has high sensitivity and specificity for diagnosing severe lumbar spinal stenosis. Its performance in diagnosing moderate and mild spinal stenosis, however, has yet to be corroborated in properly designed studies. [ABSTRACT FROM AUTHOR]

Tissue engineering has brought new possibilities for the treatment of spinal cord injury. Two important components for tissue engineering of the spinal cord include a suitable cell source and scaffold. In our study, we investigated induced mouse embryonic fibroblasts (MEFs) directly reprogrammed into neural stem cells (iNSCs), as a cell source. Three-dimensional (3D) electrospun poly (lactide-co-glycolide)/polyethylene glycol (PLGA-PEG) nanofiber scaffolds were used for iNSCs adhesion and growth. Cell growth, survival and proliferation on the scaffolds were investigated. Scanning electron microcopy (SEM) and nuclei staining were used to assess cell growth on the scaffolds. Scaffolds with iNSCs were then transplanted into transected rat spinal cords. Two or 8 weeks following transplantation, immunofluorescence was performed to determine iNSC survival and differentiation within the scaffolds. Functional recovery was assessed using the Basso, Beattie, Bresnahan (BBB) Scale. Results indicated that iNSCs showed similar morphological features with wild-type neural stem cells (wt-NSCs), and expressed a variety of neural stem cell marker genes. Furthermore, iNSCs were shown to survive, with the ability to self-renew and undergo neural differentiation into neurons and glial cells within the 3D scaffolds in vivo. The iNSC-seeded scaffolds restored the continuity of the spinal cord and reduced cavity formation. Additionally, iNSC-seeded scaffolds contributed to functional recovery of the spinal cord. Therefore, PLGA-PEG scaffolds seeded with iNSCs may serve as promising supporting transplants for repairing spinal cord injury (SCI). [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Epidemiological studies show that patients with Alzheimer's disease (AD) have an increased risk of developing osteoporotic hip fracture. However, whether abnormal amyloid beta peptide (Aβ) deposition, one of the pathological hallmarks of AD, also occurs in osteoporosis and the relationship between Aβ and human osteoporosis remain unknown. This study addressed these issues. Methods: Forty-five female patients (osteoporosis 21, osteopenia 16 and normal 8) with osteoporotic/traumatic vertebral compression fractures were enrolled and Aβ42 and amyloid precursor protein (APP) levels assessed in the biopsy specimens of vertebral trabecular bone using immunohistochemistry (IHC) staining and semi-quantitative evaluation assays. Spearman rank correlation analysis was applied to explore the association between Aβ42/APP levels and the corresponding bone mineral density (BMD). Moreover, immunofluorescent assays and laser scanning confocal microscopy assays were used to examine the expression patterns of Aβ42/APP in patient bone tissues and osteocytes. Additionally, eight female patients with osteoporotic/traumatic femoral neck fractures, including two control patients were selected and Aβ42 and APP were identified in the femoral necks by RT-PCR and Western blotting (WB) assays. Next, a rat model of ovariectomy-induced osteoporosis was created and we evaluated Aβ42 and APP expression differences in the proximal tibia by IHC and RT-PCR and WB assays in comparison with a sham-operation group. Finally, the RAW264.7 cell line and human bone marrow monocyte (hBMMC) derived osteoclasts and human Aβ42 co-culture assays were performed to investigate the effect of Aβ42 on osteoclasts cell viability, number, differentiation and activation by the Cell Counting Kit-8 assay, tartrate resistant acid phosphatase staining assay, RT-PCR assay measuring the lytic gene expression and hydroxyapatite resorption assay respectively. Results: The mRNA and protein expression levels of Aβ42 and APP were elevated remarkably in the osteoporotic bone tissues both from human and ovariectomized rats when compared with the age-/sex-matched controls. Moreover, the expression levels had a negative correlation with corresponding BMD in patients (RAβ42 =−0.617, p <0.0001; RAPP =−0.531, p =0.0002). In addition, Aβ42 was located mainly in the membrane and cytoplasm of osteocytes and in the extracellular matrix, while APP was largely located in the membrane of the osteocytes. Finally, Aβ42 can potently enhance osteoclasts differentiation and activation but had no effect on osteoclasts cell viability or number (dose- and time-dependency did not exist and oligomerization of Aβ42 was not a prerequisite in the osteoclastogenesis assay). Conclusions: Aβ is relevant to human osteoporosis and may have an important role in the pathogenesis of osteoporosis. [Copyright &y& Elsevier]

Neural stem cells (NSCs)-based regenerative medicine provides unprecedented therapeutic potential in neural insults. However, NSC-based neurogenesis is strongly influenced by the inflammatory environment after injury, which is mainly modulated by macrophages' secretion effects. In this study, we adopted poly L-lactic acid (PLLA) aligned fibers to guide macrophages elongating along the fiber directions and polarizing phenotypically toward anti-inflammatory M2 type. 7,8-DHF was loaded within the fibers with a sustained and controlled release pattern to promote the polarization of the macrophages and secretion of various anti-inflammatory factors. NSCs showed enhanced neuronal differentiation in the presence of the conditioned medium (CM) from M2 macrophages cultured on the 7,8-DHF-loaded PLLA aligned fibers. Moreover, M2-CM promoted neurogenesis by enhancing neurite outgrowth of NSC-derived neurons. In summary, we provided a novel therapeutic strategy for NSC neurogenesis by manipulating macrophage classification into anti-inflammatory M2 phenotypes with the 7,8-DHF-loaded PLLA aligned fibers, existing potential applications in treating neural injuries. • We provided a strategy of manipulating macrophage polarization toward M2 phenotypes by aligned fibers loaded 7,8-DHF. • Macrophages of elongated morphology tended to secrete pro-inflammatory factors. • M2-CM promoted neuronal differentiation and neurite outgrowth of neural stem cell. • NSC neurogenesis can be promoted by manipulating macrophage classification into anti-inflammatory M2 phenotypes. [ABSTRACT FROM AUTHOR]

• Analysis of ceRNA networks involved in the subacute stage of SCI were lacking. • Genes (Flna, ID3, HK2) and TFs (Sp1, Trp53, Jun, Rela) are involved in SCI. • lncRNAs (Neat1, Xist, Malat1) are significant in the epigenetic mechanisms of SCI. • miRNAs (miR-16-5p, miR-1958, miR-185-5p) play critical roles in SCI. • These biomarkers could be therapeutic targets for treating SCI at subacute stage. This study aims to investigate the genetic and epigenetic mechanisms involved in the pathogenesis of subacute stage of spinal cord injury (SCI). Gene-expression datasets associated with SCI were downloaded from the Gene Expression Omnibus (GEO) database, and differential expression analyses were performed in order to identify differentially expressed genes (DEGs). Multiple network types were constructed and analyzed, including protein–protein-interaction (PPI) network, miRNA-target network, lncRNA-associated competing endogenous RNA (ceRNA) network, and miRNA-transcription factor (TF)-target network. Cluster analyses were performed to identify significant modules. To verify the prediction accuracy of the in-silico identified molecules, qRT-PCR experiments were conducted. The results depicted the Ywhae gene as the hub gene with the highest degree in the PPI network. The ceRNA network identified specific genes (Flna, ID3, and HK2), miRNAs (miR-16-5p, miR-1958, and miR-185-5p), and lncRNAs (Neat1, Xist, and Malat1) as playing critical regulating roles in the pathological mechanisms of SCI. The miRNA-TF-gene interaction network identified four important TFs (Sp1, Trp53, Jun, and Rela). The miRNA-gene-TF interaction loops from the significant modules indicated that miR-325-3p can interact with the Asah1 gene and TF-Sp1 by forming a closed loop. The qRT-PCR experiments verified four selected genes (Flna, ID3, HK2, and Ywhae) and two selected TFs (Jun, and Sp1) as significantly up-regulated following SCI. The results indicated that four genes (Flna, ID3, HK2, and Ywhae), four transcription factors (Sp1, Trp53, Jun, and RelA), two miRNAs (miR-16-5p and miR-325-3p), and three lncRNAs (Neat1, Xist, and Malat1) are likely to be involved in the molecular mechanisms underlying the subacute stage of SCI. These findings uncover putative pathogenic mechanisms involved in SCI and might bear translation significance for future research towards therapeutic development. [ABSTRACT FROM AUTHOR]

Background: Circulatory osteocalcin (OC) has been widely used as a biomarker to indicate bone turnover status in postmenopausal osteoporosis (PMO). However, the change of serum OC (sOC) level in PMO cases compared to postmenopausal controls remains controversial.Methods: We searched the online database of PubMed and Cochrane Library. A meta-analysis of case-control studies was performed to compare the pooled sOC level between PMO patients and postmenopausal controls. Subgroup analysis according to potential confounding factors (different OC molecules and regions of the study population) was also performed.Results: Ten case-control studies with 1577 postmenopausal women were included in this meta analysis. We found no significant difference in the pooled sOC level [mean difference (MD) = 1.84, 95% confidence interval (CI): (- 1.49, 5.16), p = 0.28] between PMO patients and controls. Subgroup analysis also revealed no significant difference in intact OC [MD = 1.76, 95%CI: (- 1.71, 5.23), p = 0.32] or N-terminal mid-fragment of the OC molecule [MD = 0.67, 95%(- 5.83, 7.18), p = 0.84] between groups. For different regions, no significant difference in sOC was found in Asian population between cases and controls [MD = -0.06, 95%(- 6.02, 5.89), p = 0.98], while the pooled sOC level was significantly higher in European PMO cases than controls [MD = 3.15, 95%(0.90, 5.39), p = 0.006].Conclusions: Our analysis revealed no significant difference in sOC level between PMO cases and controls according to all the current eligible studies. OC molecules are quite heterogeneous in the circulation and can be influenced by glucose metabolism. Therefore, sOC is currently not a good indicator for the high bone turnover status in PMO. More trials with standardized methodologies for the evaluation of circulatory OC are awaited to update our current findings. [ABSTRACT FROM AUTHOR]

Background The minimally invasive lateral transpsoas approach allows retroperitoneal access for discectomy and graft placement. However, the procedure has rarely been used for the treatment of septic spondylodiscitis. The purposes of this study were to evaluate the clinical and radiographic outcomes from this minimally invasive procedure for septic spondylodiscitis. Methods Thirty-one consecutive patients (17 males and 14 females) were included in this study from July 2013 to January 2016. Clinical outcomes were assessed by Oswestry Disability Index, visual analog scale, modified Macnab criteria, and inflammatory parameters. Radiographic results were analyzed by studying the changes in diseased disc height, lordosis, and fusion status. Results The Oswestry Disability Index and visual analog scale score improved by 58% and 69% at the last follow-up. The modified Macnab criteria were found to be excellent in 21 patients (68%) and good in 10 (32%). Inflammatory parameters normalized over the average 24 months follow-up. There were no major complications that might have influenced the outcomes in this cohort. A complete fusion after 12 months was achieved in 87% of patients. A mean 7.5 mm restoration in disc height and 6.4° restoration in lumbar lordosis were observed in all patients, whereas an average 4.5 mm loss in restored height resulting from graft subsidence was observed in 24 patients during the follow-up. However, graft subsidence did not influence clinical outcomes significantly. Conclusions A minimally invasive lateral transpsoas approach in combination with instrumentation provides a novel treatment for patients with septic spondylodiscitis without severe kyphosis and neurologic impairment. [ABSTRACT FROM AUTHOR]

Objective To compare the effectiveness and safety of decompression alone (D group) with decompression and fusion (DF group) for patients who were diagnosed with lumbar degenerative spondylolisthesis (LDS). Methods Electronic databases were searched for relevant studies that compared decompression alone with decompression and fusion for LDS. Then, data extraction and quality assessment were conducted, and the extracted data were analyzed by using RevMan 5.3. We used the random effects model for studies that had heterogeneity between them, and for those without heterogeneity, the fixed model was used. Results Four randomized controlled trials and 14 nonrandomized controlled studies involving 77,994 patients were included for this meta-analysis. Although the DF group was associated with a higher postoperative change score on a visual analog scale compared with the D group in terms of back ( P = 0.02) and leg ( P = 0.04), they failed to reach the minimum clinically important difference. Moreover, no significant differences were found in Oswestry Disability Index, European Quality of Life–5 Dimensions, Short-Form 36 physical and mental component summaries score, and patients' satisfaction ( P > 0.05) between treatment groups. Complication rate and reoperation rate ( P > 0.05) were similar in both groups. Data analysis also showed that the DF group was associated with longer operation time ( P < 0.00001), more intraoperative blood loss ( P < 0.00001), and longer length of hospital stay ( P < 0.00001). Conclusions Among patients with LDS, decompression and fusion surgery did not yield better clinical outcomes than decompression alone surgery. Also, the complication rate and reoperation rate were comparable between treatment groups. However, patients who had undergone decompression alone had shorter operation time, less intraoperative blood loss, and shorter hospital stay. [ABSTRACT FROM AUTHOR]